SUMMARY:We quantified microvessel morphology and vascular endothelial growth factor (VEGF) expression in human colonic carcinoma with or without metastasis. The cancerous growth and the noncancerous section of surgical specimens from 36 patients with colorectal carcinoma (14 without metastasis and 22 with metastasis) were studied. Tissue slices immunostained with CD34 were processed for microvessel counts (per mm 2 ), the mean diameter of microvessels ( m), and the mean spatial direction of microvessels (degree), defined by the angle between the longitudinal axis of microvessels and the direction perpendicular to the surface of the mucosa. Tissue slices immunostained with anti-VEGF antibody were processed for total epithelial cell counts (per mm 2 ), VEGF-positive cell counts (per mm 2 ), and VEGF-positive ratio (%). Carcinoma without metastasis had significantly larger microvessel counts (213 Ϯ 77, p Ͻ 0.01), larger microvessel diameter (7.99 Ϯ 1.77, p Ͻ 0.05), and larger spatial direction (47.2 Ϯ 8.3, p Ͻ 0.01) than normal tissue (144 Ϯ 49 for microvessel counts; 7.03 Ϯ 0.90 for microvessel diameter; 39.5 Ϯ 6.6 for spatial direction). Compared with carcinoma without metastasis, carcinoma with metastasis had a significantly larger microvessel diameter (9.75 Ϯ 2.65, p Ͻ 0.03) and lower microvessel counts (180 Ϯ 92, p ϭ 0.51). Carcinoma without metastasis had a significantly larger VEGF-positive cell count (1276 Ϯ 805, p Ͻ 0.05) and larger VEGF-positive ratio (53.6 Ϯ 39.3, p Ͻ 0.05) than normal tissue (571 Ϯ 553 for VEGF-positive cell counts; 24.6 Ϯ 23.2 for VEGF-positive ratio). Carcinoma with metastasis had a significantly lower total cell count (1443 Ϯ 237, p Ͻ 0.001) and lower VEGF-positive cell count (716 Ϯ 463, p Ͻ 0.05) than carcinoma without metastasis. With tumor progression, microvessel diameter significantly increased and microvessel counts decreased, which can be in part explained by VEGF expression. The microvessel diameter seems to be the dominant parameter responsible for cancer cell intravasation as the first step of metastasis. (Lab Invest 2002, 82:555-562).
Aim: Atherosclerosis can be evaluated by carotid intima media thickness (IMT), the aortic calcification index (ACI), and pulse wave velocity (PWV). We investigated which test was most closely related to cerebro-and cardiovascular disorders (CCVD) in hemodialysis patients. Methods: Maximum IMT (max-IMT), ACI, and PWV were examined in 110 hemodialysis patients, using carotid ultrasonography, abdominal CT and a blood pressure pulse wave instrument, respectively. Blood hemoglobin A1c (HbA1c), serum total cholesterol, high density lipoprotein cholesterol, triglyceride, total protein, albumin, high sensitivity C reactive protein (hs-CRP), and tumor necrosis factor a were measured. The patients were divided into two groups; with and without CCVD and the degree of atherosclerosis was evaluated in each group. Results: Compared to the CCVD (-) group, the CCVD (+) group showed significantly higher percentages of males and diabetic patients, higher levels of HbA1c (5.14 vs 4.83%) and hs-CRP (0.320 vs 0.167 mg/dL), an older age group (64.5 vs 57.5 years), a greater max-IMT (2.05 vs 1.19 mm), and a higher ACI (71.8 vs 41.0%); and significantly lower diastolic blood pressure (82.8 vs 89.2 mmHg). Multiple logistic regression analysis showed that the factors influencing the development of CCVD were age (odds ratio: 1.092), ACI (odds ratio: 1.025), and max-IMT (odds ratio: 2.006). However, PWV did not significantly relate to CCVD. Conclusions: In hemodialysis patients, the ACI and max-IMT were significantly associated with CCVD, but the association of PWV was weak. A prospective cohort study is warranted to determine the risk factors for CCVD in hemodialysis patients.
The degree of mucosal redness can be quantified as an index of hemoglobin (IHB) that changes with photographic conditions. The first aim of the present study was to stress the exclusion of γ correction as a critical procedure for reliable measurements of IHB. The second aim was to characterize Matts grade by pictorial parameters in the gray scale picture of IHB and to establish a computer‐aided grading system of endoscopic severity in ulcerative colitis. A total of 130 digital endoscopic pictures of 55 patients with ulcerative colitis (30 Matts 1, 70 Matts 2, 20 Matts 3 and 10 Matts 4) were used. The pictures without γ correction were processed for the mean IHB, SD of IHB, kurtosis of IHB and contrast feature. A computer‐aided grading system was constructed on the basis of Bayes decision theory. Significant increase in the mean IHB was seen when comparing Matts 1 to Matts 2. The SD of IHB or contrast feature significantly increased from Matts 2 to Matts 3 or from Matts 3 to Matts 4. Kurtosis of IHB was significantly larger in Matts 3 than in Matts 1 or Matts 4. Sensitivity and specificity when discriminating Matts 1 from Matts 2, Matts 2 from Matts 3 and Matts 3 from Matts 4 by the grading system were found to be 84 and 96%, 94 and 70%, and 100 and 85%, respectively. The computer‐aided grading system may permit quantitative evaluation of effects of treatments in ulcerative colitis with minimal interobserver variation.
To examine whether or not intraluminal pressure changes at a site in the human colon reflect with fidelity the local bowel wall contractions or relaxation, endoscopic recording of the changes in colonic calibre as a parameter of the motor events with simultaneous manometry was performed at a fixed site in a prepared sigmoid colon during the interdigestive state. In four of the 12 subjects, a total of 20 phasic pressure waves with an amplitude of 13-22 mmHg and a duration of 13-18 sec were obtained in a 20 min recording session. Eighteen of the 20 phasic pressure waves (90%) were associated not with a decrease (contraction) but with an increase in the calibre (relaxation). The pressure change began 0.2-8.4 sec (mean: 4.5 sec) behind and ended-1.8 to 8 sec (mean: 3.5 sec) ahead of the calibre change. In the other eight subjects, no phasic pressure change was recorded in the presence of an overt calibre change. We conclude that manometric phasic pressure change recorded at a site in the empty human colon is not necessarily correlated with the localized contractile activity. Extrapolation of pressure profiles in the colon to motor events at the manometric site should be cautious.
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